Virus-encoded proteases, which are essential for viral replication, are required for the processing of viral protein precursors. Interference with the processing of protein precursors inhibits the formation of infectious virions. Accordingly, inhibitors of viral proteases may be used to prevent or treat chronic and acute viral infections. Darunavir has HIV protease inhibitory activity and is particularly well suited for inhibiting the HIV-1 and HTV-2 viruses. Chemically darunavir is (1S,2R,3′R,3′aS,6′aR)-[3′-hexahydrofuro[2,3-b]furanyl-[3-(4-aminobenzenesulfonyl)isobutylamino]-1-benzyl-2-hydroxypropyl]carbamate. Darunavir is represented by the following structure:

Processes for the preparation of darunavir were disclosed in EP 715618, WO 99/67417, U.S. Pat. No. 6,248,775, and in Bioorganic and Chemistry Letters, Vol. 8, pp. 687-690, 1998, “Potent HIV protease inhibitors incorporating high-affinity P2-ligands and (R)-(hydroxyethylamino)sulfonamide isostere”, all of which are incorporated herein by reference.
Darunavir can exist in different polymorphic forms, which differ from each other in terms of stability, physical properties, spectral data and methods of preparation.
U.S. Patent Publication No. 2005/0250845 described pseudopolymorphs of darunavir including Form A (ethanolate), Form B (hydrate), Form C (methanolate), Form D (acetonate), Form E (dichloromethanate), Form F (ethylacetate solvate), Form G (1-ethoxy-2-propanolate), Form H (anisolate), Form I (tetrahydrofuranate), Form J (isopropanolate) and Form K (mesylate) of darunavir. Pseudopolymorphs are distinguished from polymorphs and defined as crystalline forms having solvent molecules incorporated into the crystalline lattice.
One object of the present disclosure is to provide novel solvated forms of darunavir and processes for their preparation.
Another object of the present disclosure is to provide a novel composition and process for pure amorphous darunavir pharmaceutical compositions comprising them.